Purpose: To review the evidence about screening for vitamin D deficiency in adults.
Data Sources: MEDLINE, Embase, the Cochrane Library, trial registries, and other sources through March 12, 2020; bibliographies from retrieved articles, outside experts, and surveillance of the literature through November 30, 2020.
Study Selection: Two investigators independently selected studies using a priori inclusion and exclusion criteria. We selected randomized, controlled trials (RCTs) that evaluated the benefits or harms of screening or treatment of vitamin D deficiency in adults; observational studies were also eligible for selection if they reported eligible harms. For treatment, we selected studies for which at least 90 percent of the population had serum vitamin D levels less than 30 ng/ml. We excluded studies with poor methodological quality and studies conducted in developing countries.
Data Extraction and Analysis: One investigator extracted data and a second checked accuracy. Two reviewers independently rated methodological quality for all included studies using predefined criteria. When at least three similar studies were available, meta-analyses were conducted.
Data Synthesis: We did not identify any studies directly evaluating health benefits or harms of screening. We included 46 studies (45 RCTs and 1 nested case-control study within a RCT) that evaluated various doses, frequency, and duration of treatment with vitamin D (with or without calcium). We assessed 13 studies as good quality; the rest were fair quality.
Twenty-six RCTs and one nested case-control study reported on the effectiveness of treatment on health outcomes; half enrolled or reported on participants with serum vitamin D levels less than 20 ng/ml. Overall, the evidence suggests treatment with vitamin D (with or without calcium) had no effect on most health outcomes, though the evidence is limited for some outcomes. Among community-dwelling populations, treatment had no effect on mortality (pooled absolute risk difference [ARD] 0.3% [95% confidence interval [CI], −0.6% to 1.1%]; 8 RCTs), fractures (pooled ARD −0.3% [95% CI, −2.1% to 1.6%]; 6 RCTs), incidence of diabetes (pooled ARD 0.1% [95% CI, −1.3% to 1.6%]; 5 RCTs), incidence of cardiovascular disease (2 RCTs, relative risk 1.00 [95% CI, 0.74 to 1.35] and 1.09 [95% CI, 0.68 to 1.76]), incidence of cancer (2 RCTs, hazard ratio 0.97 [95% CI, 0.68 to 1.39] and 1.01 [95% CI, 0.65 to 1.58] , or depression (3 RCTs, various measures reported). The evidence for the impact of treatment on falls was inconclusive. The pooled ARD for incidence of participants with one or more falls was −4.3% (95% CI, −11.6% to 2.9%; 6 RCTs), and the pooled incidence rate difference for the total number of falls per group was −0.10 (95% CI, −0.19 to −0.002). The evidence was mixed for the impact of treatment on physical functioning (2 RCTs) and limited for the impact on infection (1 RCT).
The incidence of total adverse events, serious adverse events, discontinuations due to adverse events, kidney stones, and other harms was similar between active treatment and control groups.
Limitations: Only English-language studies were included. Most studies were primarily designed to assess intermediate health outcomes; some studies were conducted in nondeficient populations but reported on subgroups with deficiency. We did not assess comparative effectiveness or harms of various doses or formulations of vitamin D or assess the impact of vitamin D treatment for specific clinical conditions.
Conclusions: No studies have evaluated the direct benefit or harms of screening for vitamin D deficiency. Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D (with or without calcium) has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events. The evidence is inconclusive about the impact of treatment on physical functioning and infection.